JPH02191216A - Drug for fish parasite - Google Patents

Abstract

PURPOSE: To obtain a medicine for preventing parasites on fishes, especially parasitic protozoan and metazoa by including a substituted 1,2,4-triazinediones or a salt thereof. CONSTITUTION: This medicine for preventing parasites on fishes includes a compound of the formula [R<1> is an aromatic group or a heterocyclic aromatic group bonded by C; X is O, S, SO, SO2 or C(CN)H; R<2> is H, a halogen, NO2 , an alkyl, an alkoxy, a halogenoalkyl or an halogenoalkoxy; R<3> is H, an alkyl, an alkenyl, an alkynyl or an aralkyl] or a base salt thereof, e.g. 2-chloro-α-(4- chlorophenyl)-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)-phenyla cetonitrile. The treatment by the medicine is performed by an addition to a food, a short period treatment by a transcutaneous bath (the concentration is 5-10mg/L) when transferring the fishes between feeding vessels or a temporary or permanent pool treatment (the concentration is 0.1-5mg/L).

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method for treating fish parasites, particularly parasitic protozoa (single-celled organisms) and metazoa (multicellular organisms).
．． The present invention relates to a drug containing 4-triazinediones.

The protozoa and metazoa include common classes of fish parasites. In large-scale animal husbandry in large-scale fish farms, the parasite poses a serious problem as infestations can spread quickly to all organisms.

These parasites pose a major problem in the breeding of fish, especially young and susceptible fish, and cause considerable losses.

Some parasitic protozoa and metazoa attach to fish skin and cod, thus causing skin damage and making it susceptible to bacterial, viral, or fungal infections. They are also vectors of viral infection. Some parasitic protozoa and metazoa also infect the internal organs of fish (eg intestines, bones), causing growth deformities or death of the fish.

Few agents are known for controlling parasitic protozoa and metazoa. However, their effects are not always satisfactory. Moreover, they only have a narrow spectrum of action against certain parasites. Other parasites such as Myxozoa or Microsporidia (Micr).

No drugs are available that act against 5por id ia).

The following general formula (I) R1 represents an optionally substituted aromatic group or an optionally substituted heteroaromatic group bonded to a carbon atom; N X is o, s, so, so, or -CH-; R1 represents - or more, same- or different groups selected from the group consisting of hydrogen, halogen, nitro, alkyl, alkoxy, halogenoalkyl, halogenoalkoxy; R3 is hydrogen , optionally substituted alkyl, alkenyl, alkynyl, aralkyl.
．． 4-triazinediones, and their base salts, are effective against fish parasites, especially parasitic protozoa and metazoa, such as P lathelminthes.
It has been found that it can be used for the control of s).

Some triazinediones are listed in the European Patent Publication Specification (E
P-O3) No. 170.316, and they are also the subject of an unpublished prior application by the applicant.

The following general formula (I) R1 represents an optionally substituted heteroaromatic group bonded to a carbon atom; X represents o, s, so, so; R2 represents hydrogen, halogen, nitro, R3 represents hydrogen, optionally substituted alkyl, alkenyl, alkynyl, aralkyl; Substituted 1.2.4-triazinediones are represented by the following a) formula (n), where X represents O or S; R2 and R3 have the above meanings; m) R'-A (I[[) where R1 has the above meaning; A is a group: halogen, -o-sow-alkyl, -0-S
O,-halogenoalkyl, -0-SO,-aryl, -
5-alkyl; b) Production of a compound represented by formula (I) in which R" does not represent hydrogen is carried out using the following formula (Ia), where R', R" , X represents a compound represented by the following formula (IV) R3-B (IV) where R3 represents optionally substituted alkyl, alkenyl, alkynyl, aralkyl; B is halogen, -0- SO, -alkyl, -0-SO,
-aryl, -0-SO2-halogenoalkyl; or c) production of a compound of formula (I) in which It can be produced by a production method in which a compound represented by formula (I) in which S represents S is reacted with an oxidizing agent;

It is obtained by heating and decarboxylating a compound represented by the following formula (II), where X, R", and R3 have the above meanings.

In the formula (V), X represents 0 or S; RJt represents - or more, same- or different groups selected from the group consisting of halogen, nitro, alkyl, alkoxy, halogenoalkyl, halogenoalkoxy ,X
When represents S, it further represents hydrogen: R3 represents hydrogen, alkyl, alkenyl, alkynyl, aralkyl The compound represented by is new, and in the following formula (V), X
represents 0 or S; R2 represents - or more, same or different groups selected from the group consisting of halogen, nitro, alkyl, alkoxy, halogenoalkyl, halogenoalkoxy;
When represents S, it further represents hydrogen; R3 represents hydrogen, alkyl, alkenyl, alkynyl, aralkyl The compound represented by is new, and in the following formula (Vl),
A compound represented by is obtained by heating in the presence of aqueous acid.

Formula (Vl) In the formula, X, R'', R', R' have the above meanings: R'' represents alkyl or optionally substituted aryl; R7 is hydrogen or optionally substituted 1C alkyl, -C - for aryl is obtained by heating in the presence of a base.

The compound represented by the formula (■) in which X, R'', R', R'l:! having the above meaning is new, and in the following formula (■), X
, R'', R3, R', R' and R' have the above meanings,
When R7 represents H or X represents S, R2 represents R which can further represent hydrogen; , R' has the above meaning; is diazotized with an alkali metal nitride in the presence of an aqueous mineral acid, and the reaction product is then converted into the following formula (I[) R'-CH,-GO -N-COOR-(I[)S In the formula, R'', R' and R1 have the above meanings: Obtained by reacting with a compound represented by the following.

The compound represented by formula (I) which is preferably used is such that RI is optionally halogen-, alkyl-, cyano-, nitro-10-
Alkyl-S-alkyl-, halogenoalkyl-substituted phenyl, thiazolyl, oxasilyl, benzothiazolyl or benzoxacylyN X represents O, S or -CH-; R2 represents halogen or Cl-8-alkyl; R3 represents represents hydrogen or Ct-C4-alkyl, especially methyl.

In the compound represented by the formula (I) which is particularly preferably used, CN alkyl, especially mef) k,C,-a-halogenoalkyl,
Especially trifluoromethyl, norogen especially chlorine, bromine,
substituted with fluorine, nitro, CN-C5-a-alkoxy, especially methoxy, Cl-4-halogenoalkoxy, especially trifluoromethoxy, C,,-alkylthio, especially methylthio, Cl-4-halogenoalkylthio, especially trifluoromethylthio R1 represents hydrogen or a group selected from the group consisting of halogen, especially chlorine, bromine, C11-alkyl, especially methyl; and R3 represents hydrogen.

Very particularly preferably used compounds of formula (I) are those in which X represents 0; R1 represents optionally chlorine-, methyl-1- or trifluoromethyl-substituted thiazolyl or benzothiazolyl; , methyl or chlorine -
or more groups; Rs represents hydrogen;

Other compounds of formula (I) which are particularly preferably used are those in which CN X represents -CH-; R1 represents phenyl optionally substituted with chlorine-, methyl-1 or trifluoromethyl- ,; R3 is selected from the group consisting of hydrogen, chlorine or methyl;
represents the same or different or more groups; R3 represents hydrogen or methyl;

Particular examples include the following compounds: 2-chloro-a-(4-chlorophenyl)-4-(4,
5-dihydro-3,5-dioxo-1゜2.4-)riazin-2(3H)-yl)-phenylacetonitrile and 2.6-'; chloroσ-(4-10lophenyl)-4
-(4,5-dihydro-3,5-dioxo-1,2,4
-triazin-2(3H)-yl)-7enylacetonitrile.

Furthermore, the following compounds are exemplified: R8 R a p heat 3-CH, 6-C12 3CH36-CF@ 3-CH,5-C(2 3,5-CQ 6-CM 3.5-C126-CF.

3.5-CQ 5-CM Further mention may be made of the following compounds: -CQ -Br -F 6-CH.

-0CH3 6-No.

-CN -CF3 6-3CF.

6-OCF.

-CQ -Br -F 6-CH.

-0CH3 3CH3 CH3 3cHs -CQ -CQ -CQ -CQ 3’-CQ 3’-(I 3'-C12 3'-C12 3'-CQ 3'-CQ 3'-C(I 3'-(I 3', 5'-Cff 3', 5'-CM 3', 5'-C(2 X=-0 R3Rt 6-NO□ 6-No.

-5CF3 -Cff -Br -F -CH5 6-OCH.

6-No.

-CN -CF3 6-SCF.

-0CF3 -0ff -Br -CH3 R1X -0 3', 5'-C12 3', 5'-CQ 3', 5'-Cff 3', 5'-C1+ 3', 5'-Cff 3'-CQ.

5’-CHs 3'-CQ.

5’-c Hs 3'-CQ, 5’-c Hs 3'-CQ.

5’-c Hs 3'-CQ.

5’-CHs 3'-CQ.

5’-CH3 3'-CQ.

5'-CH.

R,R.

6-OCH.

6-No.

-CN -3CF3 -0CF3 -CI2 -Br -F 6-OCH3H -CN -CN X-OR R 3'-(I゜ 5’-CHs 3'-CQ.

5'-CH.

3’-ca, 5'-C) 1m 3'-CH3, 5'-CH3 3'-CH5, 5'-CH5 3’-〇Hz, -CH3 3'-C11 3'-CH3 3'-CL 5'-CH.

3'-CQ.

5’-CQ 6-CF3 -5CF3 -CQ -ca -cm -Ci2 -C11 -Ca -CQ ca -Cg -CQ X-ORs 3'-Br 3'-Br.

5'-Br 3'-CF.

3'-CF3. 5'-ca 3'-ca.

5'-cm 3'-CH.

3'-CQ, s'-ca 3'-CH.

R,R 6-Cff H 6-(l　　H 6-(l　　H 8-Cl1 H -ca 6-CQH CH, 6-CQ H -C! H@ -Cm 3'-CQ 3'-C12 3'-CQ 3'-CH.

3'-CH.

3'-CHl 3'-CQl 5’-CQ 3'-cm.

5’-CQ CQ 3'-CL 5’-C11 ca 3'-CQ.

5’-CQ 3'-CH5 3'-CI2 5'-(I ca CF3 CH.

3'-CH.

3'-CQ 5’-C11 3'-CH.

H.C.Q. CH,CQ C,H,Crt C.F.

In the production method, if 2.2-(3,5-dichloro-4-hydroxyphenyl)-1,2,4-triazine-3,5-(2H,4H)dione is employed as compound ■, 2.6 -dichlorobenzothiazole of the formula (III
), the process can be expressed by the following reaction formula.

946c).

The compound represented by formula (II) when R8 represents a group other than hydrogen is novel.

Preferred compounds of formula (II) are those in which R2 and R3 have the meanings given as preferred in the compounds of formula (I).

The novel compounds represented by the following formula 1) are exemplified.

death! The formula in which R1 and R3 represent hydrogen The compound is known (J, 5I Unio Pa1acki ac, Rerum, Nat.

23), 39-45; c.

(n) ouka, Ac t a 01omuk, F 1984 (Chem. A, 102 203 -CQ -CH3 3,5-CI2 3-CH,,5-CHs 3.5-CH.

The substituted heterocycle represented by formula (III) is known or can be produced in a similar manner to a known method (Beilste
in Vo+, 27; Katrizky and Rees
,ComprehensiveHet,Chem,Co
1.6 1984).

They have the preferred meanings given above for the compounds of formula (I). Compounds represented by the following formula ([1) may be exemplified.

S 6-(I S 5.6-(I 06-CQ 0 5.6-Cl2 s 4-ca cmS
4.5-(l C(I04-CQ C
Q o 4.5-CIl (I reaction is preferably carried out using a diluent.

Suitable diluents for this manufacturing method are virtually all inert organic solvents. These are preferably aliphatic and aromatic, optionally halogenated hydrocarbons, benzine, ligroin, benzene, toluene, xylene, methylene chloride, ethylene chloride, chloro-7-olm,
carbon tetrachloride, chlorobenzene and 0-dichlorobenzene, ethers such as diethyl ether and dibutyl ether, glycol dimethyl ether and diglycol dimethyl ether, tetrahydro7rane and dioxane,
Ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone, esters such as methyl acetate and ethyl acetate, nitriles such as acetonitrile and propionitrile, amides such as dimethylformamide, dimethylacetamide and N-methylpyrrolidone, and dimethyl Includes sulfoxide phosphoric triamide.

The reaction is carried out in the presence of an inorganic or organic acid acceptor.

Examples of acid acceptors are: alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, alkali metal carbonates and alkali metal alkoxides such as sodium carbonate, potassium carbonate,
Sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, as well as aliphatic, aromatic or heterocyclic amines such as triethylamine, pyridine, 1,5-diazabicyclo-[4,3.01-
Non-5-ene (DBN), 1,8-diazabicyclo-[5.4,OJ-undec-7-ene (DBU)
and 1,4-diazabicyclo-[2,2.

2]-octane (DABCO).

The reaction is carried out at a temperature of 50°C to 200°C, preferably 80°C.
It is carried out at a temperature of ~160°C under atmospheric pressure or elevated pressure.
The reaction is preferably carried out under atmospheric pressure.

The reaction is carried out in one of the diluents already mentioned for formulas (II) and (II).
) are combined in equimolar amounts and the mixture is heated. Once the reaction is complete, the reaction mixture is acidified using a dilute inorganic acid (eg hydrochloric acid) and the precipitate formed is filtered, washed and dried.

In process 2b for the production of compounds of formula (I) when R3 does not represent hydrogen, 2-[4-[
2'-Benzothiazolyloxy]phenyl] 1.
2.4-triazine-3.5-(2H.

4H)-dione as the compound represented by formula (I a) and methyl iodide as the compound represented by formula (IV), the process is represented by the following reaction formula % Formula % Formula % Formula (Ia) The compound to be produced is new, and production method 2
Obtained as described in a.

Compounds represented by formula (IV) are known or can be produced by known methods. Methyl iodide and ethyl bromide may be mentioned in particular.

The reaction is carried out by reacting a compound represented by formula (Ia) with a compound represented by formula (mV) in the presence of a base and a diluent. Diluents that can be used are all inert organic solvents that can also be used for carrying out production method 1a.

The reaction is carried out in the presence of a base. Preferred bases include alkali metal hydroxides such as sodium hydroxide, alkali metal alkoxides such as sodium methoxide or potassium butoxide, metal hydrides such as sodium hydride, or organic bases such as 1,8-diazabicyclo[5.

4, OJ-undec-7-ene (DBU).

The reaction is carried out at temperatures between 20°C and 140°C under atmospheric pressure.

The reaction is carried out by combining equimolar amounts of the compound represented by formula (Ia) and a base, adding an equimolar amount of the compound represented by formula (IV) to the mixture, and heating the mixture to the reaction temperature. be done.

In process 2c) for the production of a compound of formula (I) -t' in which X represents one SO= or -SO,-,
-[4-(2'-Benzoxazolylthio)phenyl]'1.2.4 triazine-3.5-(2H.4
If H)-dione is taken as the compound of formula (I), the process can be described in the diagram below.

In fact, the production method can be carried out by treating a compound represented by the formula x-8 with an oxidizing agent in the presence of a diluent. Oxidizing agents include hydrogen peroxide and other inorganic peroxides, such as sodium peroxide, organic peroxoacids, such as m-chloroperbenzoic acid, and compounds of iodine and oxygen, such as sodium metaperiodite.

Diluents that can be preferably used are: alcohols, such as methanol, organic acids, such as acetic acid, and ketones, such as acetone, but also halogenated hydrocarbons, such as dichloromethane, or acid anhydrides, such as acetic anhydride. It is possible. Oxidation is carried out at temperatures between 0°C and 120°C. The pressure is preferably carried out under atmospheric pressure.

The amount of oxidizing agent can vary from 1 molar to 10 times molar. The reaction can be carried out using a compound of formula (I), x-5, together with an oxidizing agent as described above, at the reaction temperature as described above.

It is known that 1,2,4-triazinediones represented by the formula (I) in which NX represents -CH- and R1 represents phenyl can be used for controlling Coccidia in mammals and birds. was. This effect is also implied for unknown compounds represented by formula (I). Nothing is known about the possible use of compounds of formula (I) for the control of fish parasites.

Fish parasites are species of the ciliates of the protozoan sub-kingdom, such as Ichthyophthyrius multifilis (I cht
hyophthirius multifiliis
), Chilodonella ciplini (Chilodonella
cyprini), Trichodena sp, (
Trichodina spp, ), Glossatella sp, (GIossaLeNa Sp9
．． ), Epistylis sp- (Epistylis
spp, ), species of myxosporidoids, such as Myxosoma cerebralis (Myxosoma cerebralis)
ralis), Myxidium sp + (Myxidi
um spp, ), Myxoborus Sp, (
Myxobolus spp, ), Heneguya s
p.

(Heneguya 5pp-) s Hoferellus sp, (Hoferellus spp,), species of the microsporidian class, such as Gurgea sp, (Gl
ugea 5pp-), Cellophanea sp,
(Thelohania spp,), Pleistophora sp, (Pleistophora
spp, ), phylum Platyhelminthes: Trematoda: Hemizoa, e.g. Dactylogylus sp, (DactylogY
rus spp, ), Gyrodactylus sp.
, (Gyrodactylus spp,) %
Pseudodactylogillus sp, (Pseud
odacLylogyruSSpp, ), Diploz 5 p, (Diploz.

on spp, ), tapeworms, e.g.
yllaeus 1aticeps), aggregates (e.g. Diphyllopotulium sp, (Dip
hyllobo Lhrium spp, )), Tetrafolia (e.g. Phyllopotulium sp, (Phy11obo
thriu+m spp, ) and metacephalians (e.g. ProLeocephalus
) species), and various parasitic crustaceans of the phylum Arthropoda, especially the subclasses Codocuroda (fish parasites) and copepods (copepods) and isopods (isoopods) and arthropods. Includes Daphnia.

Fish includes economically useful fish, farmed fish, aquarium fish and ornamental fish of all ages living in fresh or salt water. Economically useful fish and farmed fish include carp, eel, trout, white trout,
Salmon, bream, roach, rudd, dobule
e), sole, flathead flounder, halibut, Japanese yellowtail (S eriola quinqueradiata)
), Japanese eel (Anguilla japonica)
), Red Sea Bream (Pagurus major)
, perch (D 1cenLrarchus 1ab
rax), Mullet (Mugilus cephalus)
), black porgy (poIlpano), black porgy (
S parusauratus), Tilapia species, Chichlidae 5pecies
, for example, Plagioscion.
), including spotted catfish. The medicament according to the invention is particularly suitable for treating young fish, for example carp with a body length of 24 cm. This drug is also very suitable for eel enlargement.

Treatment of fish can be done orally, for example via food, or for short periods of time (from minutes to hours) by keeping the fish in a 'medicated bath', for example when moving from one fish tank to another. It is carried out by time treatment.

However, temporary or permanent treatment of the environment in which the fish are kept (e.g. ponds, fishponds, tanks or entire tanks) is effective.

The active compounds are supplied in formulations tailored to the application.

Preparations for oral application are powders, granules, solutions, emulsion concentrates or suspension concentrates, which are homogeneously mixed with food as food additives.

The preparations are prepared in a manner known per se by combining the active compound with a solid or liquid carrier and, if appropriate, further active compounds and emulsifying or suspending agents, solubilizing agents, colorants, antioxidants and preservatives. Manufactured by mixing.

Solid carriers include, for example, natural crushed minerals such as kaolin, clay, mica, chalk, diatomaceous earth, organic carriers such as sugar,
sucrose, lactose, fructose, cereal products such as fine or coarse flour, starch, animal flour, cellulose, powdered milk, inorganic carriers such as common salts, carbonates such as calcium carbonate, bicarbonate, aluminum oxide, Includes silica and silicates.

Liquid carriers and solubilizers include water, alkanols such as ethanol, impropatol, glycols such as ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, and copolymers thereof, glycerol, and aromatic alcohols.
, such as benzyl alcohol, phenylethanol, phenoxyethanol, esters such as ethyl acetate,
Butyl acetate, benzyl benzoate, ethers such as alkylene glycol alkyl ethers such as diglopylene glycol hetmethyl ether, diethylene glycol monobutyl ether, ketones such as acetone,
Methyl ethyl ketone, aromatic and/or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, DMSO, dimethylacetamide, N-methylpyrrolidone, 2-dimethyl-4-
Includes oxymethylene-1,3-dioxalone.

Emulsifying and suspending agents: non-ion-forming surfactants, such as polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethylene stearate, Alkylphenol polyglycol ethers, amphoteric surfactants such as disodium lauryl β-iminodipropionate, or lecithin, anionic active surfactants such as sodium lauryl sulfate, fatty alcohol ether sulfates, mono/dialkyl polyglycol ethers, etc. Included are the monoethanolamine salt of sophosphate, cationically active surfactants such as cetyltrimethylammonium chloride.

In the regulator, the concentration of active compound is approximately 1 ppm to 10% by weight.

Preferred preparations for short-term treatments applied as "medicated baths" or for fish habitat treatments (pond systems), for example applied when fish migrate, exhibit an alkaline reaction upon dilution with water. - or more polar solvent solutions of the active compound.

For the preparation of such solutions, the active compound is dissolved in a polar water-soluble solvent which itself exhibits an alkaline reaction or which exhibits an alkaline reaction with the addition of alkaline water-soluble substances. The latter are preferably dissolved in the solvent as well, but they can also be suspended in the solvent in such a way that they only dissolve on contact with water. In this case, the water should have a pH of 7-10, preferably pH 8-10 after the active compound has been added.

The active compound concentration is 0.5-50%, preferably 1-25%
Possible within the % range.

All suitable solvents are aqueous solvents in which the active compound can be dissolved in sufficient concentrations and which are physiologically acceptable.

Such solvents include ethyl alcohol, isopropyl alcohol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycol, poly(oxyethylene)/poly(oxypropylene) polymers, basic alcohols such as mono-, di-, and triethanolamine, Ketones, such as acetone or methyl ethyl ketone, esters, such as ethyl lactate, and also N-methylpyrrolidone, dimethylacetamide, dimethylformamide, and also suspending and emulsifying agents, such as polyoxyethylated castor oil, polyethylene glycol sorbitan monooleate, These are polyethylene glycol stearate, polyethylene glycol ether, and polyethylene glycol alkylamine.

Exemplary bases for adjusting the alkaline pH include organic bases, such as basic amino acids, such as L- or
- arginine, L-ori, L-lysine, methylglucosamine, glucosamine, 2-amino-2-hydroxymethylpropane-(I°3)-diol, such as further N, N
, N', N''tetrakis=2-hydroxypropyl)
- ethylenediamine or polyether tetrols based on ethylenediamine (M, W, 480-420)
, inorganic bases such as ammonia or sodium carbonate (with addition of water if appropriate).

The formulation contains 0.1-20% by weight, preferably 0°1-10
May also contain weight percent of other conditioning aids such as antioxidants, surfactants, suspension stabilizers, and densifying agents such as methylcellulose, alginates, polysaccharides, galactomannans, and colloidal silica. . It is also possible to add colorants, fragrances and nutritional ingredients for animal breeding. Mention may also be made in a similar sense of acids which together with the initially introduced base form a buffer system or which reduce the pH of the solution.

The active compound concentration for application depends on the form and duration of the treatment and on the age and condition of the fish being treated. For example, for short-term treatment, the treatment time is 3-4 hours,
- 250 mg preferably 5-10 per liter of water
mg. For example, young carp are treated with a concentration of 5-10 mg/(l) for about 1-4 hours.

The eel is treated with about 5 mg/Q for about 4 hours.

Correspondingly lower concentrations are chosen when treatment times are long or when permanent treatment is carried out.

For pond treatment, water - 0. 1-5m
g of active compound is used.

A preparation for use as a food additive may have the following composition: a) Activated compound of formula (I) 1-10 parts by weight soy protein 49-90 parts by weight b) Activated compound of formula (I) Active compound 0.5-10 parts by weight Benzyl alcohol 0.08-1.4 parts by weight Hydroxypropyl methylcellulose 0-3.5 parts by weight Water to 100 parts Use as 'Medicated bath' and as pond treatment The preparation for use can have the following composition and can be prepared as follows: C) 2.5 g of the active compound of Example 4 are heated under heating for 100 m
ff dissolved in triethanolamine.

d) 2.5 g of the active compound of Example 4 and 12.5 g of lactic acid are dissolved in 100 rrl of triethanolamine under heating and stirring.

e) Dissolve 10.0 g of the active compound of Example 4 in roomQ monoethanolamine.

f) Active compound of formula (I) 5.0 g Propylene glycol 50.0 g Sodium carbonate 5.0 g 100 m with water (2 g) Active compound of formula (I) 5.0 g Monoethanolamine 10 g N-methylpyrrolidone lo
h) 2.5 g of active compound of formula (I)
Sodium carbonate 5.0 g Polyethylene glycol 200 Make up to 100 ml The active compound is dissolved in polyethylene glycol under heating and the sodium carbonate is dispersed in the solution.

Parasites of the indicated species were transferred to glass dishes containing 150 ml of water at a temperature of 22° C. and supplemented with the indicated concentration of the active compound of Example 4. After the specified time, parasites were examined under light microscopy. The observation results were as follows: Parasite concentration/time Observation of parasites Ichthyophthirius 10 ppm / Dead Ichthyophthirius multifiliis 15 minutes (Ichthyophthirius multifiliis) Pseudodactylogillus anguillae 10 ppm / Paralysis (Pse)
udodactylo-1-10 minutes gyrus ang
Example B 1n-vivo treatment of fish Gyrodactylus alcuatus
Sticklebacks heavily infested with P. lus arcuatus were treated for 1 hour at 22° C. in 2 Oa of water supplemented with 10 ppm of the active compound of Example 4. After this the fish were examined. There were no parasites present on them. The sediment contained dead or fatally injured insects.

Examples of active compounds Example 1 29 g (0,01 mol) of 2-[4-[(4″-chloro)-2′-thiacylyloxy]phenyl]-3,5(2H,4H)-dioxo-az-triazine Hydroxyphenylazauracil, 1.5 g (0.01 mol) dichlorothiazole and 1.4 g (0.01 mol) potassium carbonate are stirred under reflux in 20 mQ dry DMF for 2 hours. The reaction mixture is cooled and Acidify with HCQ and filter off the precipitated product under suction.

By ethanol reconsolidation, 2.9g (90% of theoretical value)
thiacyloxyaryl azauracil is obtained.

The following can be obtained in the same way.

Example 2 2-[4-[(4'-chloro-5'-methyl)-2
1.2.4-triazine-3,5(2H,4H)-dione Example 3 2-(4-(2-benzothiacylyloxy)-phenyl)
-1,2,4-triazine-3,5(2H.

4H)-dione Example 4 2-[4-[(6'-chloro)-2'-benzothiacylyloxy]-3,5-dichlorophenyl]-1,2,4
-Triazine-3,5(2H,4H)-dione Example 4a 2-[4-[(6'-1-lifluoromethyl)-2''-
benzothiasylyloxy] -3,5-dichlorophenyl] 1.2.4-) riazine-3,5(2H.

4H)-dione Example 4b 2-[4-[(6″-trifluoromethoxy)-2′-
benzothiazolyloxy]-3,5-dichlorophenyl]
1,2,4-triazine-3,5(2H.

4H)-dione Example 4c 2-[4-[(6'-1-lifluoromethylthio)-2
'-benzothiacylyloxy]-3,5-dichlorophenyl] 1.2.4-) riazine-3,5(2H,4H
)-dione Example 4d 2-[4-[(5',6''-dichloro)-2'benzothiacylyloxy]-3,5-dichlorophenyl]
1.2.44Ryazine-3,5(2H.

4H)-dione Example 5 2-[4-[(4'-chloro)-2'-thiacylyloxy]phenyl]-3-N-methyl-3°5- (2H
,4H)-dioxo-1,2,4-triazine. The mixture is heated to 50°C and maintained at this temperature for 3 hours. The reaction mixture is then concentrated under vacuum and the sample is added. After filtering off the solid precipitate with suction, 1.5
g (71% of theory) of n-methyl compound is obtained.

Example 6a 2-[4-[(6-chloro)-2'-benzoxasilylsul7oxyl]-3,5-dichlorophenyl]l, 2,4-triazine-3,5(2H.

4H)-Dione 2 g (6 mmol) of thiacyryloxyarylazauracil are dissolved in 20 m+2 of anhydrous DMSO and 0.14 g (6 mmol) of sodium hydride are added to the solution. The mixture was stirred for 20 minutes at reflux temperature and 5 mQ of D
1.3 g (9 mmol) of methyl iodide in MSO was mixed with 10 g (0,027 mol) of chlorobenzoxazolylthiophenyl azauracil under an argon atmosphere.
Dissolve in a mixture of mQ methanol and loOmQ dichloromethane. The mixture was cooled to lOoC and 4.6
g of m-chloroperbenzoic acid (85% strength) is added isothermally subcutaneously. Continue loh stirring at 10°C, remove the solvent under vacuum and reconstitute the residue from Improper Tool. 8.5g (
A sulfoxide of 82% of theory is obtained.

Example 6b 2-[4-(2''-Benzoxacylylsul7oxyl 4-triazine-3.5 (2H,4H)-dione Example 7 2-[4-(2''-Benzoxacylylsul7oxyl) 4-triazine-1.2.4-triazine-3.

5 (2H,4H)-dione Example 8 2-[4-[(6'-chloro)-2'-henzooxazolylsulfonyl]-3.5-dichlorophenyl3 1,2.4-triazine -3.5 (2H.

8.8 g (0.02 mol) of the 4H)-dione are dissolved in 100 ml of glacial acetic acid and the solution is stirred under reflux for 18 hours with 40 mQ of 30% strength hydrogen peroxide. After the mixture has cooled, water is added and the precipitate that has formed is filtered off with suction. 6.9 g of sulfone (theoretical value of 7
3%) is obtained.

Example 9 2-[4-(2'-benzoxasilylsulfonyl)-3,5-dichlorophenyl]l,2.4triazine-3,5(2H,4H)-dione 11)
-2-[4-(2'-benzoxasilylsulfonyl)-phenyl] 1.2.4-triazine-3゜5
(28,4H)-dione Preparation example 2 of starting material represented by formula (II) 2-(4-hydroxyphenyl)-1,2,4-triazine-3,5(
2,4H)-Dione Example of Preparation of Starting Material of Formula (V) 2-(4-Hydroxyphenyl)-3,5(2H.

4H) Dioxo-1,2,4-triazine-6-carboxylic acid 34 g (0,137 mol) of the carboxylic acid are heated at 170 DEG C. in 34 mQ of mercaptoacetic acid. After 1.5 hours, the mixture was allowed to cool, water was added, the mixture was filtered, and 24 g
(82% of theory) of the decarboxylated product is obtained.

30.1 g (0.13 mol) of cyanoazuracil are stirred under reflux for 14 hours in 1000 ml of HCQ/glacial acetic acid (I:l). The mixture was allowed to cool and concentrated;
Water is added to the residue and the precipitated product is filtered off under suction (I9
g, 59% of theory).

Production example of starting material represented by formula (Vl) 2-(4-hydroxyphenyl)-3,5-(2H,4H)dioxo-
43.8 g (0,158 mol) of 6-dia2-1,2,4-triazine
), 8.

5 g (0,213 mol) of NaOH are refluxed in 400 mff of absolute ethanol for 2 hours. The mixture is subsequently cooled, acidified with hydrochloric acid and concentrated under vacuum. - Stir the bath with water and filter off the precipitated product with suction. After drying, 30.
1 g (85% of theory) of cyanozauracil is obtained.

Production example of starting material represented by formula (■) Ethyl-N-[[[cyano(4-hydroxyphenyl)
-Hydrazinylidene 1-methyl]-carbonyl]-carbamate 10 g (0,091 mol) of 4-hydroxyaniline are dissolved in concentrated HC (I19,7 mff) and 200 mQ of glacial acetic acid, and the solution is added to 6.4 g (0°) in 30 mQ of water. 092 mol) sodium nitrite solution is added dropwise at 0-5°C. Stirring is continued until a clear solution is formed and 14.3 g (
0,092 mol) of cyanoacetyl urethane and 21 g (
0.25 mol) of sodium acetate is added and 1
Continue stirring at 0°C for 3 hours. The reaction mixture is concentrated under vacuum, water is added and the solid is filtered off with suction. Thus 19g
(75%) of the product is obtained as a microcrystalline yellow powder.

Preferred embodiments of the present invention include the following.

1. The following general formula (I) In the formula, R1 represents an optionally substituted aromatic group or an optionally substituted heteroaromatic group bonded to a carbon atom; N X is o , s, so, so, or -CH-; R'' represents water, 1 halogen, nitro, alkyl, alkoxy,
Represents one or more same or different groups selected from the group consisting of halogenoalkyl and halogenoalkoxy; R3 represents hydrogen, optionally substituted alkyl, alkenyl, alkynyl, aralkyl; 2.4
- Use of triazinediones and their base salts for controlling fish parasites.

2. A drug against fish parasites, which contains at least one 1,2°4-triazinedione represented by formula (I) according to item 1.

3. 1.2. for controlling fish parasites, characterized in that l,2°4-triazinedione represented by formula (I) according to item 1 is applied to fish and/or their habitats.
Use of 4-1-riadinedione.

4. A method for producing a drug against fish parasites, which comprises mixing l,2°4-triazinedione represented by formula (I) according to item 1 with a filler and/or a surfactant.

5. Utilization of l,2°4-triazinedione represented by formula (I) according to item 1 for the production of a drug against fish parasites.

Claims (1)

[Claims] 1. The following general formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) In the formula, R^1 is an aromatic group that may be optionally substituted, or a bond with a carbon atom represents an optionally substituted heteroaromatic group with Represents one or more same or different groups selected from the group consisting of alkyl, alkoxy, halogenoalkyl, and halogenoalkoxy; R^3 is hydrogen, optionally substituted alkyl, alkenyl,
Use of substituted 1,2,4-triazinediones represented by alkynyl, aralkyl, and their base salts for controlling fish parasites.